From the Guidelines
Multaq (dronedarone) 400mg twice daily is generally safe for atrial fibrillation management in patients without severe heart failure or permanent atrial fibrillation, but requires careful patient selection. According to the most recent study 1, antiarrhythmic drugs like dronedarone increase the risk of bradycardia and AVB, and should be monitored with ECG and serum K+ and Mg2+ levels. The study also recommends avoiding dronedarone in patients with severe heart failure, as it may increase the risk of fatal hepatotoxicity.
Key considerations for patient selection include:
- Avoiding use in patients with NYHA Class III-IV heart failure, recent decompensated heart failure, permanent atrial fibrillation, significant liver or lung disease, or QT prolongation
- Monitoring liver function tests at baseline and periodically during treatment
- ECG monitoring for QT prolongation
- Avoiding grapefruit juice and certain medications that interact with dronedarone, including strong CYP3A4 inhibitors, QT-prolonging drugs, and certain statins
Common side effects of dronedarone include gastrointestinal issues, fatigue, and skin reactions. The 2022 study 1 provides guidance on monitoring and recommendations for antiarrhythmic drugs, while the 2016 study 1 discusses rate control therapy in atrial fibrillation, but does not directly address the safety of Multaq 400mg BID. Overall, careful patient selection and monitoring are essential to minimize the risks associated with dronedarone use.
From the FDA Drug Label
WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION In patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure; MULTAQ doubles the risk of death. In patients with permanent atrial fibrillation, MULTAQ doubles the risk of death, stroke and hospitalization for heart failure. MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure. MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm.
The safety of Multaq 400mg BID for atrial fibrillation is a concern due to the increased risk of:
- Death
- Stroke
- Heart failure in patients with decompensated heart failure or permanent atrial fibrillation. Multaq is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure, and in patients in atrial fibrillation who will not or cannot be cardioverted into normal sinus rhythm 2.
From the Research
Safety of Multaq 400mg BID for Atrial Fibrillation
- The FDA has approved dronedarone (Multaq) for the oral treatment of atrial fibrillation and flutter, as stated in the study 3.
- Dronedarone is chemically similar to amiodarone but has a different pattern of short-term adverse effects, including more gastrointestinal disorders but less frequent thyroid disorders, neurological disorders, hypersensitivity reactions, hypertension, and QT prolongation 4.
- Common adverse effects of dronedarone include diarrhoea, nausea and vomiting, and cutaneous disorders, as well as transient elevation of creatinin levels and cases of renal failure 4.
- The efficacy of dronedarone has been investigated in several clinical trials, proving its effect in the prevention of AF recurrence, rate control in paroxysmal/persistent and permanent AF, reduction of cardiovascular hospitalization or death from any cause 5.
- Dronedarone is contraindicated in severe or deteriorating heart failure, as shown in the ANDROMEDA trial 6.
- The ATHENA trial demonstrated that dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation 6.
- However, dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm, as shown in the DIONYSOS trial 6.
Comparison with Amiodarone
- Amiodarone is the most effective drug for atrial fibrillation but has considerable toxicity 3.
- Dronedarone has a lower antiarrhythmic efficacy compared to amiodarone but may have a better safety profile 4, 5.
- Indirect comparisons and one head-to-head study indicate that the relative safety of dronedarone may be at a cost of its lower antiarrhythmic efficacy compared with amiodarone 5.
Renal Function
- Kidney function is a known predictor of cardiovascular morbidity and mortality, and patients with atrial fibrillation often have kidney dysfunction 7.
- Elimination of AF by catheter ablation was associated with improvement of kidney function over a 1-year follow-up in patients with mild to moderate kidney dysfunction 7.
- Dronedarone has been associated with transient elevation of creatinin levels and cases of renal failure 4.